1. |
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2. |
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3. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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4. |
- Dork, T, et al.
(author)
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Two truncating variants in FANCC and breast cancer risk
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524-
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Journal article (peer-reviewed)abstract
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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5. |
- Boutet, S., et al.
(author)
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High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography
- 2012
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 337:6092, s. 362-364
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Journal article (peer-reviewed)abstract
- Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.
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6. |
- Arnlund, David, et al.
(author)
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Visualizing a protein quake with time-resolved X-ray scattering at a free-electron laser
- 2014
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In: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:9, s. 923-926
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Journal article (peer-reviewed)abstract
- We describe a method to measure ultrafast protein structural changes using time-resolved wide-angle X-ray scattering at an X-ray free-electron laser. We demonstrated this approach using multiphoton excitation of the Blastochloris viridis photosynthetic reaction center, observing an ultrafast global conformational change that arises within picoseconds and precedes the propagation of heat through the protein. This provides direct structural evidence for a 'protein quake': the hypothesis that proteins rapidly dissipate energy through quake-like structural motions.
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7. |
- Barty, A., et al.
(author)
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Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements
- 2012
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In: Nature Photonics. - 1749-4885 .- 1749-4893. ; 6:1, s. 35-40
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Journal article (peer-reviewed)abstract
- X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis1. For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information1, 2, 3, 4. Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology5 should enable structural determination from submicrometre protein crystals with atomic resolution.
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8. |
- Botvinik-Nezer, Rotem, et al.
(author)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Journal article (peer-reviewed)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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9. |
- Pedersoli, E., et al.
(author)
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Mesoscale morphology of airborne core-shell nanoparticle clusters : x-ray laser coherent diffraction imaging
- 2013
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In: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 46:16 SI, s. 164033-
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Journal article (peer-reviewed)abstract
- Unraveling the complex morphology of functional materials like core-shell nanoparticles and its evolution in different environments is still a challenge. Only recently has the single-particle coherent diffraction imaging (CDI), enabled by the ultrabright femtosecond free-electron laser pulses, provided breakthroughs in understanding mesoscopic morphology of nanoparticulate matter. Here, we report the first CDI results for Co@SiO2 core-shell nanoparticles randomly clustered in large airborne aggregates, obtained using the x-ray free-electron laser at the Linac Coherent Light Source. Our experimental results compare favourably with simulated diffraction patterns for clustered Co@SiO2 nanoparticles with similar to 10 nm core diameter and similar to 30 nm shell outer diameter, which confirms the ability to resolve the mesoscale morphology of complex metastable structures. The findings in this first morphological study of core-shell nanomaterials are a solid base for future time-resolved studies of dynamic phenomena in complex nanoparticulate matter using x-ray lasers.
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10. |
- Loh, N. D., et al.
(author)
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Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 486:7404, s. 513-517
-
Journal article (peer-reviewed)abstract
- The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology(1) to climate science(2), yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate(3); visible light scattering provides insufficient resolution(4); and X-ray synchrotron studies have been limited to ensembles of particles(5). Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source(6) free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins(7), vibrational energy transfer by the hydrodynamic interaction of amino acids(8), and large-scale production of nanoscale structures by flame synthesis(9).
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11. |
- Alves, G., et al.
(author)
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USING A 3-TIER TRAINING MODEL FOR EFFECTIVE EXCHANGE OF GOOD PRACTICES IN AN ERASMUS plus PROJECT
- 2018
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In: 12TH INTERNATIONAL TECHNOLOGY, EDUCATION AND DEVELOPMENT CONFERENCE (INTED). - : IATED-INT ASSOC TECHNOLOGY EDUCATION & DEVELOPMENT. - 9788469794807 ; , s. 6392-6400
-
Conference paper (peer-reviewed)abstract
- VISIR+ is an Erasmus+ project that aims to develop educational modules for electric and electronic circuits theory and practice following an enquiry-based teaching and learning methodology. The project has installed five new VISIR remote labs in Higher Education Institutions located in Argentina and Brazil, to allow students doing more experiments and hence acquire better experimental skills, through a combination of traditional (hands-on), remote and virtual laboratories. A key aspect for the success of this project was to motivate and train teachers in the underpinning educational methodology. As such, VISIR+ adopted a 3-tier training process to effectively support the use of VISIR in the Institutions that received it. This process is based on the "train the trainer" approach, which required the participating partner institutions to identify and engage a number of associated partners, interested in using their newly installed remote lab. To measure the quality of the training process, the same satisfaction questionnaire was used in all training actions. This paper presents a detailed description of the training actions along with the analysis of the satisfaction questionnaire results. Major conclusions are that the quality level of the training process remained practically the same across all training actions and that trainees sometimes considered the practical use of the VISIR remote lab as difficult, irrespectively of where and when the training action took place.
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12. |
- Banys-Paluchowski, M, et al.
(author)
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Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:7
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Journal article (peer-reviewed)abstract
- In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).
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13. |
- Duane Loh, N., et al.
(author)
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Profiling structured beams using injected aerosols
- 2012
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In: Proceedings of SPIE. - : SPIE. - 9780819492210 ; , s. 850403-
-
Conference paper (peer-reviewed)abstract
- Profiling structured beams produced by X-ray free-electron lasers (FELs) is crucial to both maximizing signal intensity for weakly scattering targets and interpreting their scattering patterns. Earlier ablative imprint studies describe how to infer the X-ray beam profile from the damage that an attenuated beam inflicts on a substrate. However, the beams in-situ profile is not directly accessible with imprint studies because the damage profile could be different from the actual beam profile. On the other hand, although a Shack-Hartmann sensor is capable of in-situ profiling, its lenses may be quickly damaged at the intense focus of hard X-ray FEL beams. We describe a new approach that probes the in-situ morphology of the intense FEL focus. By studying the translations in diffraction patterns from an ensemble of randomly injected sub-micron latex spheres, we were able to determine the non-Gaussian nature of the intense FEL beam at the Linac Coherent Light Source (SLAC National Laboratory) near the FEL focus. We discuss an experimental application of such a beam-profiling technique, and the limitations we need to overcome before it can be widely applied.
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14. |
- Alves, G. R., et al.
(author)
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A sustainable approach to let students do more real experiments with electrical and electronic circuits
- 2018
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In: SIXTH INTERNATIONAL CONFERENCE ON TECHNOLOGICAL ECOSYSTEMS FOR ENHANCING MULTICULTURALITY (TEEM'18). - New York, NY, USA : Association for Computing Machinery. - 9781450365185 ; , s. 508-514
-
Conference paper (peer-reviewed)abstract
- The present paper focus on the use of remote laboratories in higher education from a sustainability viewpoint. The particular case of engineering education, and, within it, the more specific subject of experiments with electrical and electronic circuits is presented first, to then discuss the benefits of using remote labs, while considering the three dimensions of sustainable development, i.e.: economic practice, environmental protection, and social integration. The paper debates how remote labs address each dimension. © 2018 Copyright is held by the owner/author(s). Publication rights licensed to ACM.
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15. |
- Chapman, Henry N, et al.
(author)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
-
Journal article (peer-reviewed)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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16. |
- Felgueiras, C., et al.
(author)
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A sustainable approach to laboratory experimentation
- 2019
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In: TEEM'19: SEVENTH INTERNATIONAL CONFERENCE ON TECHNOLOGICAL ECOSYSTEMS FOR ENHANCING MULTICULTURALITY. - New York, NY, USA : Association for Computing Machinery. - 9781450371919 ; , s. 500-506
-
Conference paper (peer-reviewed)abstract
- Sustainability is currently a general concern in society and in particular in the use of laboratories for educational purposes. Although laboratories are unavoidable facilities for education, they often produce waste resulting from students' experiments. To contribute for sustainable solutions in education, the use of remote laboratories instead of the traditional hands-on laboratories should be considered in every engineering course. It is precisely this aspect that is discussed in the current paper. Some comments about the importance of sustainability in education are made. Later, it is described the use of a remote laboratory named VISIR in a course held at the Polytechnic of Porto - School of Engineering, for the conduction of an electronic experiment named Schmitt Trigger. At the end, some comments about the contribution of this remote lab for sustainability in education, are provided. © 2019 ACM.
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17. |
- Martin, A. V., et al.
(author)
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Femtosecond dark-field imaging with an X-ray free electron laser
- 2012
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In: Optics Express. - 1094-4087. ; 20:12, s. 13501-13512
-
Journal article (peer-reviewed)abstract
- The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.
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18. |
- Martin, A. V., et al.
(author)
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Noise-robust coherent diffractive imaging with a single diffraction pattern
- 2012
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In: Optics Express. - 1094-4087. ; 20:15, s. 16650-16661
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Journal article (peer-reviewed)abstract
- The resolution of single-shot coherent diffractive imaging at X-ray free-electron laser facilities is limited by the low signal-to-noise level of diffraction data at high scattering angles. The iterative reconstruction methods, which phase a continuous diffraction pattern to produce an image, must be able to extract information from these weak signals to obtain the best quality images. Here we show how to modify iterative reconstruction methods to improve tolerance to noise. The method is demonstrated with the hybrid input-output method on both simulated data and single-shot diffraction patterns taken at the Linac Coherent Light Source. (C) 2012 Optical Society of America
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19. |
- Rolles, D., et al.
(author)
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Femtosecond x-ray photoelectron diffraction on gas-phase dibromobenzene molecules
- 2014
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In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 47:12
-
Journal article (peer-reviewed)abstract
- We present time-resolved femtosecond photoelectron momentum images and angular distributions of dissociating, laser-aligned 1,4-dibromobenzene (C6H4Br2) molecules measured in a near-infrared pump, soft-x-ray probe experiment performed at an x-ray free-electron laser. The observed alignment dependence of the bromine 2p photoelectron angular distributions is compared to density functional theory calculations and interpreted in terms of photoelectron diffraction. While no clear time-dependent effects are observed in the angular distribution of the Br(2p) photoelectrons, other, low-energy electrons show a pronounced dependence on the time delay between the near-infrared laser and the x-ray pulse.
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20. |
- Aquila, Andrew, et al.
(author)
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Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
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In: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
-
Journal article (peer-reviewed)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
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21. |
- Bogan, M. J., et al.
(author)
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Single-shot femtosecond x-ray diffraction from randomly oriented ellipsoidal nanoparticles
- 2010
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In: Physical Review Special Topics - Accelerators and Beams. - 1098-4402. ; 13:9, s. 094701-
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Journal article (peer-reviewed)abstract
- Coherent diffractive imaging of single particles using the single-shot "diffract and destroy" approach with an x-ray free electron laser (FEL) was recently demonstrated. A high-resolution low-noise coherent diffraction pattern, representative of the object before it turns into a plasma and explodes, results from the interaction of the FEL with the particle. Iterative phase retrieval algorithms are used to reconstruct two-dimensional projection images of the object from the recorded intensities alone. Here we describe the first single-shot diffraction data set that mimics the data proposed for obtaining 3D structure from identical particles. Ellipsoidal iron oxide nanoparticles (250 nm x 50 nm) were aerosolized and injected through an aerodynamic lens stack into a soft x-ray FEL. Particle orientation was not controlled with this injection method. We observed that, at the instant the x-ray pulse interacts with the particle, a snapshot of the particle's orientation is encoded in the diffraction pattern. The results give credence to one of the technical concepts of imaging individual nanometer and subnanometer-sized objects such as single molecules or larger clusters of molecules using hard x-ray FELs and will be used to help develop robust algorithms for determining particle orientations and 3D structure.
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22. |
- Johansson, Henrik J., et al.
(author)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2019
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
Journal article (peer-reviewed)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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23. |
- Loh, N. D., et al.
(author)
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Cryptotomography : Reconstructing 3D Fourier Intensities from Randomly Oriented Single-Shot Diffraction Patterns
- 2010
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:22, s. 225501-1-225501-5
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Journal article (peer-reviewed)abstract
- We reconstructed the 3D Fourier intensity distribution of monodisperse prolate nanoparticles using single-shot 2D coherent diffraction patterns collected at DESY's FLASH facility when a bright, coherent, ultrafast x-ray pulse intercepted individual particles of random, unmeasured orientations. This first experimental demonstration of cryptotomography extended the expansion-maximization-compression framework to accommodate unmeasured fluctuations in photon fluence and loss of data due to saturation or background scatter. This work is an important step towards realizing single-shot diffraction imaging of single biomolecules.
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24. |
- Lomb, Lukas, et al.
(author)
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Radiation damage in protein serial femtosecond crystallography using an x-ray free-electron laser
- 2011
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 84:21, s. 214111-1-214111-6
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Journal article (peer-reviewed)abstract
- X-ray free-electron lasers deliver intense femtosecond pulses that promise to yield high resolution diffraction data of nanocrystals before the destruction of the sample by radiation damage. Diffraction intensities of lysozyme nanocrystals collected at the Linac Coherent Light Source using 2 keV photons were used for structure determination by molecular replacement and analyzed for radiation damage as a function of pulse length and fluence. Signatures of radiation damage are observed for pulses as short as 70 fs. Parametric scaling used in conventional crystallography does not account for the observed effects.
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25. |
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